Farmworkers are frequently exposed to a wide variety of pesticides, including organophosphate, carbamate, and pyrethroid insecticides, all of which are neurotoxins. The doses of pesticides to which farmworkers are generally exposed, while frequent, are small. Therefore, the full effect of these neurotoxic pesticides may go undetected for years until manifest as a diagnosis of neurodegenerative disease. Research is needed to delineate the immediate, sub-clinical neurological signs of pesticide exposure among farmworkers. CPBR allows communities and universities to conduct research collaboratively and to address policy and regulatory changes. This project is based on established collaborations between Wake Forest University School of Medicine, North Carolina Farmworkers Project, HOLA of Wilkes County, and Toxic Free NC. This CBPR project will accomplish 5 specific aims: (1) delineate differences in pesticide exposure between Latino farmworkers who are exposed to agricultural pesticides and Latino manual workers who are not exposed to agricultural pesticides;(2) determine associations between pesticide exposure and neurologic function;(3) delineate the effects of pesticide exposure on changes in neurologic function among pesticide exposed Latino farmworkers and non-exposed Latino manual workers;(4) characterize the DNA methylation and gene expression patterns in pesticide exposed Latino farmworkers and non-exposed Latino manual workers, and determine if changes in neurologic function are associated with DNA methylation and gene expression patterns, and (5) address pesticide safety and health policy and regulatory changes through collaboration with members of the farmworker community, farmworker health and immigrant health advocacy groups, and policy makers and regulators. This project is significant and innovative. It includes a sufficiently large sample size, a long follow-up time, and appropriate neurological domains to evaluate the weight of evidence for neurological effects from pesticide exposure. It examines dose-response relationships for a set of biomarkers of pesticide exposure in an attempt to establish quantitative estimates of neurological outcomes. It combines multiple methods, including neurobehavioral, neurophysiological, and genomics. It provides a unique opportunity to study several clinically salient and important public health outcomes that are potentially responsive to interventions. It examines genetic factors involving metabolism of pesticides and genome-wide DNA methylation with etiological importance in the expression of neurological dysfunctions. This genomics-based approach is likely to identify associations with, and potentially the underlying mechanisms of, pesticide exposure and neurological function. This project is innovative in its attention to policy. It will follow a large cohort of adult farmworkers with an appropriate comparison group to document pesticide exposure and outcomes over multiple years. We have included policy change as an integral component and we will integrate policy development throughout the project. PUBLIC HEALTH RELEVANCE: Chronic, low-level pesticide exposure is pervasive in the United States, and it is particularly prevalent among Latino migrant and seasonal farmworkers. Substantial research has documented the potential effects of pesticide exposure for human neurological health. Based on data collected with migrant and seasonal farmworkers, this CBPR study will determine the association of pesticide exposure with neurological health and the biological mechanisms underlying this association.